髓系Tet2-IL-1β轴通过限制儿茶酚胺能刺激肠嗜铬细胞分化来调节肠道炎症，这一成果由芝加哥大学Bana Jabri课题组经过不懈努力而取得。相关论文于2025年11月3日发表在《免疫学》杂志上。

研究团队发现，骨髓特异性缺失的10 - 11易位甲基胞嘧啶双加氧酶2 （TET2）通过限制肠染色质（EC）细胞分化和随后的血清素释放来预防结肠炎。这种保护作用是由髓样细胞产生的白细胞介素(IL)-1β升高介导的，髓样细胞在炎症条件下向酪氨酸羟化酶（TH）阳性神经元发出信号。神经元IL-1R信号抑制神经元-上皮相互作用和随之而来的α-肾上腺素能信号，从而减少EC分化。相反，生理应激通过增强儿茶酚胺能信号加重结肠炎，从而增加粘膜损伤后EC的分化和血清素的产生。因此，髓源性IL-1β和应激通过α1-肾上腺素能-EC轴，揭示了形成肠道炎症的神经免疫上皮回路。

据介绍，破译多细胞相互作用对于理解免疫介导的疾病至关重要。髓细胞可以协调炎症反应，并且是与神经元、上皮细胞和基质细胞的免疫串扰的中心。

附：英文原文

Title: A myeloid Tet2-IL-1β axis modulates intestinal inflammation by restricting catecholaminergic stimulation of enterochromaffin cell differentiation

Author: Deepika Sharma, Ankit Malik, Veronica Locher, Shaina McGrath, Sarah Zabala, Hardik Grover, Cezary Ciszewski, Li Chen, Daping Yang, Isaac M. Chiu, Bana Jabri

Issue&Volume: 2025-11-03

Abstract: Deciphering multicellular interactions is essential to understanding immune-mediated diseases. Myeloid cells can coordinate inflammatory responses and are central to immune crosstalk with neuronal, epithelial, and stromal cells. Here, we show that myeloid-specific loss of ten-eleven-translocation methylcytosine dioxygenase 2 (TET2) protected against colitis by limiting enterochromaffin (EC) cell differentiation and subsequent serotonin release. This protective effect was mediated by elevated interleukin (IL)-1β production by myeloid cells, which signals to tyrosine hydroxylase (TH)-positive neurons under inflammatory conditions. Neuronal IL-1R signaling dampened neuronal-epithelial interactions and consequent α-adrenergic signaling, thereby reducing EC differentiation. Conversely, physiological stress exacerbated colitis by enhancing catecholaminergic signals, which increased EC differentiation and serotonin production following mucosal injury. Thus, myeloid-derived IL-1β and stress exert opposing control over colitis severity through the α-adrenergic-EC axis, uncovering a neuro-immune-epithelial circuit that shapes intestinal inflammation.

DOI: 10.1016/j.immuni.2025.10.012

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00467-4